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Concept: Diabetic retinopathy


Second Harmonic Generation (SHG) microscopy recently appeared as an efficient optical imaging technique to probe unstained collagen-rich tissues like cornea. Moreover, corneal remodeling occurs in many diseases and precise characterization requires overcoming the limitations of conventional techniques. In this work, we focus on diabetes, which affects hundreds of million people worldwide and most often leads to diabetic retinopathy, with no early diagnostic tool. This study then aims to establish the potential of SHG microscopy for in situ detection and characterization of hyperglycemia-induced abnormalities in the Descemet’s membrane, in the posterior cornea.

Concepts: Optics, Diabetes mellitus, Laser, Diabetes, Cornea, Diabetic retinopathy, Nonlinear optics, Descemet's membrane


OBJECTIVE: The evaluation of visual acuity (VA) in cognitively impaired older individuals may be limited by a reduced ability to cooperate or communicate. The objective of this research was to assess VA in older institutionalized individuals with cognitive impairment, including severe dementia, using various acuity charts. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Three groups of 30 participants each were recruited: (1) young participants; (2) older participants with no history of cognitive or communication disorders; and (3) older participants with cognitive impairment, including severe dementia, residing in long term care facilities. The Mini-Mental State Examination was performed for each institutionalized subject. VA was measured using 6 validated charts [Snellen, Teller cards, Early Treatment Diabetic Retinopathy Study (ETDRS)-letters, -numbers, -Patty Pics, -Tumbling Es] presented in random order. Nonparametric tests were used to compare VA scores between charts, after Bonferroni-Holm corrections for multiple comparisons. RESULTS: Participants in groups 1 and 2 responded to all charts. A large proportion of participants with dementia responded to all charts (n = 19), whereas only one did not respond to any chart. In group 3, VA charts with the lowest scores were the Teller cards (20/65) and Patty Pics (20/62), regardless of the level of dementia, whereas the highest VA scores were obtained with the Snellen (20/35) and ETDRS-letter (20/36) charts. Across all groups, the ETDRS-letter chart was the only one whose scores did not differ from those obtained with the standard Snellen chart. CONCLUSIONS: Visual acuity can be measured, and should at least be attempted, in older cognitively impaired individuals having a reduced ability to communicate.

Concepts: Dementia, Visual acuity, Ophthalmology, Diabetic retinopathy, Psychiatry, Snellen chart, Abbreviated mental test score, Charts


Although retinal neurodegenerative conditions such as age-related macular degeneration, glaucoma, diabetic retinopathy, retinitis pigmentosa, and retinal detachment have different etiologies and pathological characteristics, they also have many responses in common at the cellular level, including neural and glial remodeling. Structural changes in Müller cells, the large radial glia of the retina in retinal disease and injury have been well described, that of the retinal astrocytes remains less so. Using modern imaging technology to describe the structural remodeling of retinal astrocytes after retinal detachment is the focus of this paper. We present both a review of critical literature as well as novel work focusing on the responses of astrocytes following rhegmatogenous and serous retinal detachment. The mouse presents a convenient model system in which to study astrocyte reactivity since the Mϋller cell response is muted in comparison to other species thereby allowing better visualization of the astrocytes. We also show data from rat, cat, squirrel, and human retina demonstrating similarities and differences across species. Our data from immunolabeling and dye-filling experiments demonstrate previously undescribed morphological characteristics of normal astrocytes and changes induced by detachment. Astrocytes not only upregulate GFAP, but structurally remodel, becoming increasingly irregular in appearance, and often penetrating deep into neural retina. Understanding these responses, their consequences, and what drives them may prove to be an important component in improving visual outcome in a variety of therapeutic situations. Our data further supports the concept that astrocytes are important players in the retina’s overall response to injury and disease.

Concepts: Neuron, Retina, Retinitis pigmentosa, Diabetic retinopathy, Retinal detachment, Glial cells, Macular degeneration, Radial glia


To clarify this controversy and to provide evidence for application of lipid lowering agents in treatment of diabetic retinopathy (DR).

Concepts: Diabetes mellitus, Evidence-based medicine, Systematic review, Diabetic retinopathy, Meta-analysis


Background The relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown. Methods At 89 clinical sites, we randomly assigned 660 adults (mean age, 61±10 years) with diabetic macular edema involving the macular center to receive intravitreous aflibercept at a dose of 2.0 mg (224 participants), bevacizumab at a dose of 1.25 mg (218 participants), or ranibizumab at a dose of 0.3 mg (218 participants). The study drugs were administered as often as every 4 weeks, according to a protocol-specified algorithm. The primary outcome was the mean change in visual acuity at 1 year. Results From baseline to 1 year, the mean visual-acuity letter score (range, 0 to 100, with higher scores indicating better visual acuity; a score of 85 is approximately 20/20) improved by 13.3 with aflibercept, by 9.7 with bevacizumab, and by 11.2 with ranibizumab. Although the improvement was greater with aflibercept than with the other two drugs (P<0.001 for aflibercept vs. bevacizumab and P=0.03 for aflibercept vs. ranibizumab), it was not clinically meaningful, because the difference was driven by the eyes with worse visual acuity at baseline (P<0.001 for interaction). When the initial visual-acuity letter score was 78 to 69 (equivalent to approximately 20/32 to 20/40) (51% of participants), the mean improvement was 8.0 with aflibercept, 7.5 with bevacizumab, and 8.3 with ranibizumab (P>0.50 for each pairwise comparison). When the initial letter score was less than 69 (approximately 20/50 or worse), the mean improvement was 18.9 with aflibercept, 11.8 with bevacizumab, and 14.2 with ranibizumab (P<0.001 for aflibercept vs. bevacizumab, P=0.003 for aflibercept vs. ranibizumab, and P=0.21 for ranibizumab vs. bevacizumab). There were no significant differences among the study groups in the rates of serious adverse events (P=0.40), hospitalization (P=0.51), death (P=0.72), or major cardiovascular events (P=0.56). Conclusions Intravitreous aflibercept, bevacizumab, or ranibizumab improved vision in eyes with center-involved diabetic macular edema, but the relative effect depended on baseline visual acuity. When the initial visual-acuity loss was mild, there were no apparent differences, on average, among study groups. At worse levels of initial visual acuity, aflibercept was more effective at improving vision. (Funded by the National Institutes of Health; number, NCT01627249 .).

Concepts: Better, Clinical trial, Improve, Vascular endothelial growth factor, Retina, Ophthalmology, Diabetic retinopathy, Macular degeneration


Curcumin, the major extraction of turmeric, has been widely used in many countries for centuries both as a spice and as a medicine. In the last decade, researchers have found the beneficial effects of curcumin on multiple disorders are due to its antioxidative, anti-inflammatory, and antiproliferative properties, as well as its novel function as an inhibitor of histone aectyltransferases. In this review, we summarize the recent progress made on studying the beneficial effects of curcumin on multiple retinal diseases, including diabetic retinopathy, glaucoma, and age-related macular degeneration. Recent clinical trials on the effectiveness of phosphatidylcholine formulated curcumin in treating eye diseases have also shown promising results, making curcumin a potent therapeutic drug candidate for inflammatory and degenerative retinal and eye diseases.

Concepts: Medicine, Clinical trial, Effectiveness, Retina, Eye, Diabetic retinopathy, Macular degeneration, Curcumin


BACKGROUND: Primary vitreous floaters can be highly bothersome in some patients. In the case of persistently bothersome floaters, pars plana vitrectomy may be the most effective treatment. The aim of this study is to evaluate the incidence of complications, and patient satisfaction, after pars plana vitrectomy for disabling primary vitreous opacities. METHODS: We included a total of 110 eyes that underwent pars plana vitrectomy between February 1998 and August 2010. Fifty-seven eyes (51.8 %) underwent 20-gauge vitrectomy, whereas 53 eyes (48.2 %) underwent 23-gauge vitrectomy. In a retrospective manner, we assessed intraoperative and postoperative complications. There was a considerable range of time between surgery and questionnaire (range: 4-136 months). Patient satisfaction was assessed by a questionnaire based on a modified NEI VFQ-25 questionnaire. RESULTS: A retinal detachment occurred in 10.9 % of cases, and the incidence did not differ significantly between the 20-gauge and 23-gauge vitrectomy groups. In 4.5 % of the eyes, a retinal detachment developed within the first 3 months, and 6.4 % occurred later in the postoperative period. Cystoid macular edema occurred in 5.5 %, and an epiretinal membrane was seen postoperatively in 3.6 % of cases. Development of glaucoma requiring glaucoma surgery, a macular hole, and postoperative scotoma, each occurred in 0.9 % of cases. No cases of endophthalmitis occurred. Eighty-five percent of patients were satisfied or very satisfied with the results of the vitrectomy. Eighty-four percent of all patients were completely cured from their troublesome vitreous floaters, and an additional 9.3 % of patients were less troubled by vitreous floaters. Ten patients (9.3 %) were dissatisfied, and six of these patients (5.6 %) had a serious complication that resulted in permanent visual loss. CONCLUSIONS: Pars plana vitrectomy is an effective approach to treat primary vitreous floaters, resulting in a high rate of patient satisfaction. Postoperative complications may be more frequent than previously reported, so patients should be well-informed about the complication rate before reaching informed consent about this surgical intervention. Additional preventive measures should be considered to reduce this complication rate.

Concepts: Surgery, Medical signs, Retina, Ophthalmology, Vitrectomy, Diabetic retinopathy, Vision loss, Floater


PURPOSE:: To evaluate the anatomical and functional outcomes at 24 months in patients with diffuse diabetic macular edema treated with primary intravitreal bevacizumab (IVB) plus grid laser photocoagulation (GLP) or primary IVB alone or GLP alone. METHODS:: Retrospective, interventional, comparative, multicenter study. We included in this analysis 141 eyes of 120 patients with diffuse diabetic macular edema treated with primary IVB alone (Group A), 120 eyes of 94 patients with GLP therapy (Group B), and 157 eyes of 104 patients treated with IVB plus GLP (Group C). RESULTS:: In all 3 groups, the authors observed improvement of Early Treatment Diabetic Retinopathy Study best-corrected visual acuity from baseline to 24-month follow-up (P < 0.0001). The improvement rate in Group A was statistically significantly better than in Group B (analysis of variance, P = 0.013). The authors also found a decrease in central macular thickness in all groups from baseline to the 24-month follow-up (P < 0.0001). The comparison among 3 groups showed higher central macular thickness decrease in Group A than in Groups B and C (analysis of variance, P < 0.001). CONCLUSION:: The study provides evidence to support the use of primary IVB with or without GLP as treatment of diffuse diabetic macular edema. Primary IVB without GLP seems to be superior to GLP alone to provide stability or improvement in best-corrected visual acuity in patients with diffuse diabetic macular edema at 24 months.

Concepts: Diabetes mellitus, Vascular endothelial growth factor, Retina, Ophthalmology, Diabetic retinopathy, Analysis of variance, Laser photocoagulation, Macular edema


Abstract Purpose: To evaluate the functional and anatomical outcome after intravitreal ranibizumab injection in 2 patients with cystoid macular edema (CME) related to Irvine-Gass syndrome. Methods: Two patients with pseudophakic CME refractory to current standard topical treatment were enrolled in this study. Intravitreal (0.5 mg/0.05 mL) ranibizumab injection was performed. Baseline visits included best-corrected visual acuity (BCVA), a fundus examination, optical coherence tomography (OCT), and fundus fluorescein angiography (FA). The main outcome measures were changes in visual acuity, retinal thickness on OCT, and complications related to treatment. Results: FA and OCT confirmed the diagnosis of pseudophakic CME in both cases. The initial BCVA was 5/100 in the first case. After 1 injection of intravitreal ranibizumab, retinal edema totally regressed and BCVA improved to 6/10. The central macular thickness (CMT) measured with OCT was 379 μm at baseline and decreased to 227 μm at the 16-month visit. The initial BCVA was 5/10 in the second case. It improved to 8/10 after 2 ranibizumab injections and remained unchanged at the 21-month visit. The CMT measured with OCT was 419 μm at baseline and decreased to 243 μm at the final follow-up. There were no ocular or systemic complications related to the intravitreal injections. Conclusion: Intravitreal ranibizumab appeared to be an effective treatment of macular edema related to Irvine-Gass syndrome. Prospective controlled studies are warranted to compare the long-term safety and efficacy between intravitreal ranibizumab and other treatment options in cases of Irvine-Gass syndrome.

Concepts: Medical imaging, Medical signs, Retina, Ophthalmology, Diabetic retinopathy, Optical coherence tomography, Fluorescein angiography, Macular edema


PURPOSE: To report an association of congenital optic nerve anomalies with peripheral retina nonperfusion and to describe the clinical manifestations and treatment. DESIGN: Retrospective, observational case series. PARTICIPANTS: Fifteen patients with congenital optic nerve anomalies referred for pediatric retina consultation were studied. Sixteen eyes of 9 patients with optic nerve hypoplasia and 8 eyes of 6 patients with other congenital optic nerve anomalies, including optic nerve coloboma, morning glory disc, and peripapillary staphyloma, were included. METHODS: All patients underwent examinations under anesthesia. Wide-angle retina photographs and fluorescein angiograms were reviewed. The severity of nonperfusion was graded. The presence of fibrovascular proliferation (FP), vitreous hemorrhage (VH), and tractional retinal detachment (TRD) were documented. Anatomic outcome after treatment was recorded. MAIN OUTCOME MEASURES: Severity of nonperfusion, occurrence of secondary complications, and the anatomic outcome of patients who underwent laser treatment. RESULTS: In patients with optic nerve hypoplasia, 12 of 16 eyes (75%) had severe peripheral nonperfusion, 12 of 16 eyes (75%) had FP, 3 of 16 eyes (19%) had VH, and 10 of 16 eyes (63%) had TRD. Six of these eyes with severe nonperfusion received laser photocoagulation to the nonperfused retina; laser-treated retinas remained attached in all 6 eyes. In patients with the other optic nerve anomalies, 7 of 8 eyes (88%) had mild to moderate nonperfusion, 2 of 8 eyes (25%) had FP, 1 of 8 eyes (12%) had VH, and 2 of 8 eyes (25%) had TRD. Six of 9 patients (67%) with optic nerve hypoplasia and 1 of 6 patients (17%) with other anomalies had a coexisting congenital brain disease. CONCLUSIONS: Congenital optic nerve anomalies may be associated with peripheral retina nonperfusion and the secondary complications of FP, VH, and TRD. In this select group of patients, the nonperfusion associated with optic nerve hypoplasia seemed to be more severe and associated more frequently with secondary complications. Peripheral retina examination in eyes with optic nerve anomalies may identify nonperfusion or FP. Laser treatment of the avascular retina may have helped prevent complications from proliferative retinopathy in eyes clinically observed to have progressed or considered at risk for progression to proliferative retinopathy. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Concepts: Brain, Retina, Eye, Ophthalmology, Diabetic retinopathy, Retinal detachment, Optic nerve, Optic nerve hypoplasia